Table 1.

Correlation among HO-1 expression, aggressiveness, and outcomes in histological specimens.

Tumor	HO-1	Nrf2	Grade and Stage	Additional Markers	Metastasis, Lymph Node, Angiogenesis	Clinical and Pathological Features	Disease Outcome/Prognosis	Ref.
Positive correlation among HO-1 expression and tumor aggressiveness/poor prognosis
-Solid tumors
Astrocytoma	High level	n.e.	Grade II and III	n.e.	n.e.	n.e.	Poor OS	[163]
Clear cell renal cell carcinoma	High level	High level	No correlation with ISUP grade and T stage	n.e.	No correlation with lymph node metastasis	No significant correlation with age, gender	Poor prognosis Low MST Low post operative OS	[165]
Colangiocarcinoma	High level	n.e.	n.e.	n.e.	No association with metastasis	No significant association with age, gender, histological type	Poor OS	[166]
Gastric cancer	High level	High level	Poor differentiated tumors	Positive correlation with VEGF	Positive correlation with MVD	n.e.	n.e.	[174]
Gallbladder cancer	High level	High level	Moderately differentiated and poorly differentiated tumors (G2-G3) Correlation with Nevin classification (III-IV-V)	Positive correlation with MRP3	Metastasis	No significant correlation with gender, age, and histology type (SCC and AD)	Poor OS	[164]
Hepatocellular carcinoma	High level	n.e.	Poor differentiated tumors Edmondson-Steiner grade 2–4	n.e.	Microvascular and capsular invasion	High levels of preoperative AFP	No significant correlation with OS and recurrence	[175]
Hormone refractory prostate cancer	High level	n.e.	n.e.	n.e.	n.e.	Cancer progression	n.e.	[188]
Laryngeal cancer	High level	High level	No correlation with tumor stage (clinical stage III and IV), size tumor	High level Keap1 and NQO1	No correlation with lymph node metastasis	No correlation with age	n.e.	[189]
Melanoma	High level	n.e.	n.e.	Positive correlation with B-Raf and ERK	n.e.	n.e.	n.e.	[176]
Neuroblastoma	High level	n.e.	n.e.	n.e.	n.e.	n.e.	Poor OS	[168]
Non-muscle-invasive bladder cancer	High level	n.e.	Tumor grade G3 tumor stage pT1	Ki-67 and p53	n.e.	No significant correlation with age and gender	Poor prognosis No correlation with RFS and PFS	[161]
	High level	n.e.	Tumor grade G3 Tumor stage T1	Positive correlation with S100A4	Lymph vascular invasion	n.e.	Low RFS Low PFS	[162]
	High level	n.e.	n.e.	Positive correlation with HIF-1α	High MVD	n.e.	n.e.	[123]
	High level	High level	n.e.	Correlation with HIF-1α, HIF-2α, VEGF	n.e.	Increased serum/plasma level of IL-6, IL-8, VEGF	n.e.	[124]
Non-small cell lung cancer	High level	n.e.	Stage III-IV	Positive correlation with MMP-9	High metastatic rate	No correlation with age and gender	Poor prognosis Low OS High mortality risk	[118]
	High level	n.e.	Stage III-IV T status (T3-T4)	n.e.	Lymph node metastasis	No correlation with gender	No significant difference in patient survival between high and low staining group	[98]
Ovarian cancer	High level	n.e.	Serous undifferentiated tumors Correlation with FIGO stage (III-IV)	n.e.	Lymph node metastasis	Non optimal-debulking	Poor OS	[160]
Prostate cancer	High level	n.e.	Localized tumor	PTEN deletion	n.e.	n.e.	Relapse after radical prostatectomy	[173]
Thyroid cancer	High level	n.e.	Positive correlation with TNM (1,2,3,4) and with MACIS score	BRAFV600E mutation	No significant association with lymph node metastasis	Correlation with age and tumor aggressiveness	n.e.	[172]
-Hematopoietic tumors
Acute myeloid leukemia	High level	n.e.	n.e.	Positive correlation with HIF-1α and GLUT-1	n.e.	n.e.	Correlation with relapse and refractory	[170]
	High level	n.e.	Correleation with M5 patients	Correlation with RET gene	n.e.	Correlation with leukocytosis at diagnosis	n.e.	[167]
Chronic myeloid leukemia	Higher level in peripheral blood cells	n.e.	n.e.	n.e.	n.e.	Tumor progression	Correlation with relapse	[169]
Myelodysplastic Syndrome	High level	n.e.	Correlation with high-risk and very high-risk patients	Positive correlation with EZH2	n.e.	Progression to AML and decreased response to decitabine	n.e.	[171]
Positive correlation among HO-1 expression in tumor-associated cells and tumor aggressiveness/poor prognosis
Colorectal cancer	High level in cancer cells and in macrophages	n.e.	Stage III	n.e.	Lymph node metastasis	No significant difference between the HO-1-positive and negative with gender, age, tumor size, histological type, and depth of tumor invasion	Poor prognosis Short DSF	[179]
Glioblastoma	High level in infiltrating macrophages	n.e.	Grade IV	n.e.	Positive correlation with vascular density	n.e.	n.e.	[178]
Glioma	HO-1 positive Treg	n.e.	Correlation with grade glioma (II-III-IV)	n.e.	n.e.	n.e.	n.e.	[137]
Non-muscle-invasive bladder cancer	High level in cancer cells and fibroblast-like, tumor- infiltrating, and endothelial cells	n.e.	Correlation with high grade tumors and with stage (T1)	COX-1	MVD, LVD, PI, increased risk of metastasis	No association with age and gender	No association with recurrence	[177]
Prostate cancer	HO-1 positive macrophages infiltrate and in bone metastasis	n.e.	High-grade tumors Gleason score 7–10	n.e.	Bone metastasis	n.e.	n.e.	[117]
Negative correlation among HO-1 expression and tumor aggressiveness/poor prognosis
Colorectal cancer	High level	n.e.	Invasive CRC	Significant correlation with K-ras	n.e.	Significant correlation with normal CEA level	Better prognosis, increased MTS	[181]
	High level	n.e.	n.e.	n.e.	Low vascular invasion and lymph node metastasis	n.e.	Better survival rate	[180]
Gastric cancer	High level	n.e.	Well and moderate differentiated	n.e.	Negative lymph node metastasis	n.e.	Better prognosis	[182]
Oral squamous cell carcinoma	High level	n.e.	Well-differentiated Grade G1 No association with T stage	n.e.	Low lymph node metastasis	No association with age and sex No association with clinical stage	n.e.	[184]
Small intestinal adenocarcinoma	High level	n.e.	Low T stage (T1, T2, T3)	n.e.	Low pancreatic invasion	n.e.	Tend to have longer OS (difference not significative)	[183]
Different correlation among HO-1 expression and tumor aggressiveness/poor prognosis depending on HO-1 subcellular localization
Breast cancer	High level in malignant epithelial cells	n.e.	Grade I-II (>80%)	Positive correlation with E-cadherin	Negative correlation with lymph node metastasis	Reduced tumor size	Longer OS with increased MST	[186]
Colorectal cancer	High level in cancer cells and in stromal cells (fibroblasts, neutrophils, and macrophages)	n.e.	Well-differentiated adenocarcinoma Nuclear HO-1 localization in moderate and poor differentiated No association with TNM	n.e.	No correlation with lymph node and liver metastasis	n.e.	n.e.	[187]
Head and neck squamous cell carcinoma	High level	n.e.	High rate of HO-1 positivity in well-differentiated and moderately differentiated (<90%) Poor-differentiated high rate of nuclear HO-1	n.e.	n.e.	No association with age, gender, tumor location	n.e.	[185]

Tumors are listed alphabetically. List of table abbreviations. n.e., not evaluated; AD, adenocarcinoma; AFP, alpha feto protein; CEA, carcinoempryonic antigen; ISUP, International Society of Urologic Pathologists; LVD, lymph vascular density; MTS, median survival time; MVD, microvascular density; OS, overall survival; PI, proliferation index: PFS, progression free survival; RFS, recurrence free survival; SCC, squamous cell carcinoma.